Role of Transient Receptor Potetial Canonical Channels in Glioma Cell Biology

瞬时受体电位经典通道在胶质瘤细胞生物学中的作用

• 批准号: 7541638
• 负责人: Valerie Christine Bomben
• 金额: $ 2.98万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7541638
• 关键词: Address; Affect; Biological Models; Biology; Biopsy; Blood Vessels; Brain; Calcium; Calcium Signaling; Cations; Cell Cycle; Cell Line; Cell Proliferation; Cell Volumes; Cell physiology; Cells; Cellular Assay; Cellular biology; Clinical; Clinical Treatment; Condition; Diagnosis; Drosophila genus; Endothelial Cells; Event; Family; Glioblastoma; Glioma; Goals; Growth Factor; Imaging Techniques; Invaded; Ion Channel; Knowledge; Malignant Glioma; Malignant Neoplasms; Membrane Potentials; Microscopy; Molecular; Nutrient; Oxygen; Patients; Phospholipase C; Physiological; Play; Proliferating; Public Health; Radiation; Recombinants; Regulation; Resected; Role; Scientist; Techniques; Thinking; Time; cancer cell; cell type; chemotherapy; cranium; extracellular; in vivo Model; inhibitor/antagonist; insight; member; migration; neoplastic cell; outcome forecast; receptor; release of sequestered calcium ion into cytoplasm; tumor

DESCRIPTION (provided by applicant): Malignant gliomas are thought to be glial-dervied and present a huge clincial challenge as the median survival is under 1 year. Characteristically, they proliferate and extensively invade throughout the brain parenchyma. Other studies have shown that ion channels are involved in the proliferation and migration of glioma cells and recently the transient receptor potential canonical (TRPC) channel family has been implicated in other cell types to facilitate proliferation. Therefore, the overall goal of this study is to understand the role transient receptor potential canonical channels play in glioma cell biology. Specifically, the first aim is to characterize TRPC channels in glioma cells by expression and electrophysiological profile. To accomplish the first aim, a combination of molecular and electrophysiological techniques will be utilized. The second aim is to address the role TRPC channels play in glioma cell proliferation. To address the second aim, a variety of cellular assays will be utilized along with imaging techniques to follow the cell cycle in the context of TRPC activity. The third aim investigates how glioma cells utilize TRPC channels in their migration and proliferation along blood vessels. The third aim will employ electrophysiological technique, confocal time-lapse microscopy, and in vivo models systems. PUBLIC HEALTH RELEVANCE: Since malignant gliomas proliferate and invade throughout the brain, the prognosis for patients diagnosed is extremely poor. Studies that further investigate the mechanisms gliomas utilize to enhance proliferation and invade throughout the brain may lend new insight into clinical treatment possibilities. Therefore, scientists, clinicians, and patients will benefit from an increased knowledge of these mechanisms.

描述（由申请人提供）：恶性胶质瘤被认为是神经胶质源性的，由于中位生存期不足1年，因此在临床上具有巨大的挑战。其特点是，它们增生并广泛侵入整个脑实质。其他研究表明，离子通道参与胶质瘤细胞的增殖和迁移，最近，瞬时受体电位规范（TRPC）通道家族在其他细胞类型中参与促进增殖。因此，本研究的总体目标是了解瞬时受体电位规范通道在胶质瘤细胞生物学中的作用。具体来说，第一个目标是通过表达和电生理特征来表征胶质瘤细胞中的TRPC通道。为了实现第一个目标，将利用分子和电生理技术的结合。第二个目的是研究TRPC通道在胶质瘤细胞增殖中的作用。为了实现第二个目标，将利用各种细胞分析和成像技术来跟踪TRPC活性背景下的细胞周期。第三个目的是研究胶质瘤细胞如何利用TRPC通道沿血管迁移和增殖。第三个目标将采用电生理技术、共聚焦延时显微镜和体内模型系统。公共卫生相关性：由于恶性胶质瘤增生并侵袭整个大脑，确诊患者的预后极差。进一步研究胶质瘤促进增殖和侵袭整个大脑的机制可能为临床治疗提供新的见解。因此，科学家，临床医生和患者将受益于这些机制的知识增加。